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Mixed phenotype acute leukemia (MPAL) is a relatively rare and heterogeneous group of diseases, which account for 2-5% of leukemia. So far, no optimal treatment regimens have been established for MPAL patients. CD19 chimeric antigen receptor T (CAR T) therapy have shown remarkable efficacy in B-ALL patients. In this study, 5 MPAL patients received CD19 CAR T cell infusion and 3 out of 5 patients (60%) achieved complete response (CR). 2 of 5 patients had only mild cytokine release syndrome (CRS). Neurotoxicity was not observed. Our data indicate that CD19 CAR T therapy is safe and effective for majority refractory/relapsed (r/r) MPAL patients.

Backgrounds As CAR T-cell therapy is a highly personalized therapy, process of generating autologous CAR-T cells for each patient is complex and can still be problematic, particularly for heavily pre-treated patients and patients with significant leukemia burden. Here, we analyzed the feasibility and efficacy in 37 patients with refractory/relapsed (R/R) B-ALL who received CAR T-cells derived from related donors. Patients and Methods From April 2017 to May 2020, 37 R/R B-ALL patients with a median age of 19 years (3-61 years), were treated with second-generation CD19 CAR-T cells derived from donors. The data was aggregated from three clinical trials (www.clinicaltrials.gov NCT03173417; NCT02546739; and www.chictr.org.cn ChiCTR-ONC-17012829). Of the 37 patients, 28 were relapsed following allogenic hematopoietic stem cell transplant (allo-HSCT) and whose lymphocytes were collected from their transplant donors (3 HLA matched sibling and 25 haploidentical). For the remaining 9 patients without prior transplant, the lymphocytes were collected from HLA identical sibling donors (n=5) or haploidentical donors (n=4) because CAR-T cells manufacture from patient samples either failed (n=5) or blasts in peripheral blood were too high (>40%) to collect quality T-cells. The median CAR-T cell dose infused was 3×105/kg (1-30×105/kg). Results For the 28 patients who relapsed after prior allo-HSCT, 27 (96.4%) achieved CR within 30 days post CAR T-cell infusion, of which 25 (89.3%) were minimal residual disease (MRD) negative. Within one month following CAR T-cell therapy, graft-versus-host disease (GVHD) occurred in 3 patients including 1 with rash and 2 with diarrhea. A total of 19 of the 28 (67.9%) patients had cytokine release syndrome (CRS), including two patients (7.1%) with Grade 3-4 CRS. Four patients had CAR T-cell related neurotoxicity including 3 with Grade 3-4 events. With a medium follow up of 103 days (1-669days), the median overall survival (OS) was 169 days (1-668 days), and the median leukemia-free survival (LFS) was 158 days (1-438 days). After CAR T-cell therapy, 15 patients bridged into a second allo-HSCT and one of 15 patients (6.7%) relapsed following transplant, and two died from infection. There were 11 patients that did not receive a second transplantation, of which three patients (27.3%) relapsed, and four parents died (one due to relapse, one from arrhythmia and two from GVHD/infection). Two patients were lost to follow-up. The remaining nine patients had no prior transplantation. At the time of T-cell collection, the median bone marrow blasts were 90% (range: 18.5%-98.5%), and the median peripheral blood blasts were 10% (range: 0-70%). CR rate within 30 days post CAR-T was 44.4% (4/9 cases). Six patients developed CRS, including four with Grade 3 CRS. Only one patient had Grade 3 neurotoxicity. No GVHD occurred following CAR T-cell therapy. Among the nine patients, five were treated with CAR T-cells derived from HLA-identical sibling donors and three of those five patients achieved CR. One patient who achieved a CR died from disseminated intravascular coagulation (DIC) on day 16. Two patients who achieved a CR bridged into allo-HSCT, including one patient who relapsed and died. One of two patients who did not response to CAR T-cell therapy died from leukemia. Four of the nine patients were treated with CAR T-cells derived from haploidentical related donors. One of the four cases achieved a CR but died from infection on day 90. The other three patients who had no response to CAR T-cell therapy died from disease progression within 3 months (7-90 days). Altogether, seven of the nine patients died with a median time of 19 days (7-505 days). Conclusions We find that manufacturing CD19+ CAR-T cells derived from donors is feasible. For patients who relapse following allo-HSCT, the transplant donor derived CAR-T cells are safe and effective with a CR rate as high as 96.4%. If a patient did not have GVHD prior to CAR T-cell therapy, the incidence of GVHD following CAR T-cell was low. Among patients without a history of transplantation, an inability to collect autologous lymphocytes signaled that the patient's condition had already reached a very advanced stage. However, CAR T-cells derived from HLA identical siblings can still be considered in our experience, no GVHD occurred in these patients. But the efficacy of CAR T-cells from haploidentical donors was very poor. Disclosures No relevant conflicts of interest to declare.

The high-efficiency video coding (HEVC) standard can reduce the bit rate of compression video. However, the compression efficiency of HEVC is still challenging current internet bandwidth. This problem can be solved by reducing the number of video frames encoded by HEVC and reconstructing the reduced frames that rely on frame rate up conversion (FRUC). Unfortunately, most existing FRUC methods need to re-estimate the motion information, a step that will lead to a huge increase of video decoder complexity. An improved HEVC video compression algorithm using low-complexity FRUC is proposed based on reusing the motion vector (MV) predicted by HEVC encoding procedure to directly reconstruct the skipped frames. First, an adaptive frame-skipping scheme is used to maximize reducing the number of frames that will encode by HEVC. Second, decoder extracts the MV and residual from the received bit stream. Then an MV reliability checking and rectifying method is proposed according to adaptive residual energy analyzing. Finally, a motion-compensation method and efficient occluded area processing algorithm are proposed to reconstruct skipped frames. These methods all directly utilize the rectified MVs. Experimental results show that due to the reduced frames and decoder that does not need to re-estimate MV, the proposed method can not only significantly decrease the time of all codec procedure when comparing HEVC and other FRUC-based video compression methods but also achieve 9.7022% to 66.0030% reduction in Bjontegaard delta bit rate at low bit rates when compared to HEVC standard. In addition, the compression of the proposed method is also better than other state-of-the-art methods.

The physical properties of porous media can be more effectively observed and understood when analyzing three-dimensional (3D) structures. The use of computer-based mathematical modeling methods has been proven effective for reconstructing 3D structures of porous media from two-dimensional (2D) images. However, reconstructing a heterogeneous 3D structure from a single 2D image is currently challenging for computer-based mathematical modeling methods. Focusing on the reconstruction of heterogeneous 3D structures from a single anisotropic training image (TI), this paper first introduces a morphological completeness analysis method, which presents a completely new approach to reconstruction in which only two sections are controlled. Then, to enhance the constraint on the simulation points in this new approach to reconstruction, a double-layer and multi-grid system (DLMGS) is proposed. The updated pattern density function simulation, based on the DLMGS, is then taken as the specific reconstruction algorithm in this work. Finally, our reconstruction method is tested using a core image, and the performance of the reconstruction result is assessed using multiple functions. Detailed experiments show that our method can successfully reconstruct a heterogeneous 3D structure from a single anisotropic image, which reduces the required dimensionality of input data for 3D reconstruction and extends the applicable scope.

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov ; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn ). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients’ CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. Precis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts

With the development of the High Efficiency Video Coding (HEVC) video compression standard, there is an urgent need for more research on video format transcoding from H.264/Advanced Video Coding (AVC) to HEVC. In this paper, we highlight the difference between the inter-prediction mechanisms of the two standards, and propose detailed steps to complete bit stream transcoding from H.264/AVC to HEVC. In the transcoding process, we use information extracted from the H.264/AVC decoder in conjunction with our proposed algorithm, called "merging smaller blocks into a larger one" (MSBLO), to accurately obtain information regarding the coding unit (CU) size and the motion vector (MV), along with the prediction mode of the prediction unit (PU). This ultimately reduces the computational complexity of the determination of the optimum inter-prediction mode in the transcoding process. Experimental results show that our proposed transcoding algorithm reduces the computational complexity of the current HEVC model by approximately 90% with a lower rate distortion loss of coding efficiency.

Compared with H.264/AVC, the latest High Efficiency Video Compression Standard (HEVC) saved nearly 50% bit-rate with same video quality. However, the compression efficiency of HEVC is still unsatisfactory. In order to further enhance the compression performance of HEVC. In this paper, a new frame rate up-conversion technology combined with HEVC is proposed. At decoder side, we utilize the information in HEVC transmitted bit-stream to classify the motion vector predicted by HEVC into reliable and unreliable categories. The reliable category is directly used to interpolate skipped frames and unreliable category are re-estimated. Finally, the skipped frames are compensated by above motion vectors. The experimental results confirm the effectiveness of the proposed algorithm in this paper.

The Use of computer-based mathematical modeling method has been proven effective for reconstructing 3D structures from a 2D training image (TI). In order to reconstruct the 3D structure of heterogeneous media from a single TI with special morphological characteristics, a 3D reconstruction algorithm based on morphological completeness analysis of TI is proposed in this paper. By analyzing the completeness of TI, this algorithm obtains a matching 3D reconstruction method. For TI with local special morphological features, the morphological completeness should adopt a 3D reconstruction method that only controls one section. In the specific process of reconstruction, this paper presents concrete measures including feature extraction, image restoration and specific reconstruction, etc. At last, the quantitative analysis using four functions including two-point correlation function, linear path function, chord length distribution function and local porosity function shows that the reconstruction structure is well similar to TI (referring to the 3D structure) in terms of quantitative features, and the 3D reconstruction method proposed in this paper is very effective.

Three-dimensional (3D) digital images are helpful in studying the physical properties of a medium. Moreover, reconstructing a 3D image from a two-dimensional (2D) image via computer-mathematical modeling is an important process. Based on the relationship between cascaded grids, an ingenious cascaded polymorphic method is proposed in this work to reconstruct a 3D image from a 2D image. By using the cascaded polymorphic method, a patch can be copied directly into a reconstruction grid by matching the patterns between cascaded grids; the polymorphism of the templates correspond to the grid size. To improve the reconstruction performance further, the non-edge region expansion strategy for a layer and the non-edge region replication strategy for adjacent layers were also proposed. A core sample and building material were selected as the test materials, and several effective measurements were used as quantitative means. To display the reconstruction effect intuitively, 2D reconstruction experiments were also performed along with the 3D experiment. The results show that the reconstruction speed is significantly improved using the cascaded polymorphic method, and the morphological features of the 3D reconstruction are clearly promoted.

The video sequence restoration described in this article has been extended to many areas of our lives today. People use it to perform various restoration tasks, making it possible for some pictures that were impossible to restore in the past. This paper uses experimental methods to study the error concealment and traditional image restoration in video compression, and mainly studies the CDD model algorithm, TV model algorithm and error mode. This article also has a very important meaning for the related research of video communication error control, that is, the research of digital image restoration technology, in the post-processing of film and television works, the fuzzification of network video, and the restoration of old documentaries.

Introduction Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated promising efficacy in patients with relapsed and refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CART remains a major issue. Here, we analyzed the factors related to long-term efficacy, including overall survival (OS), leukemia-free survival (LFS) and cumulative relapse rate (CRR), following CAR-T therapy in 231 R/R B-ALL patients who achieved complete remission (CR) within one month after CAR T-cell therapy. Patients and Methods From April 2017 to March 2019, 254 patients with R/R B-ALL were enrolled onto one of five different clinical trials (NCT03173417; ChiCTR-ONC-17012829; NCT02546739; ChiCTR1800016541; and NCT03671460) at our center and received a second generation CD19+ CAR T-cell infusion. The median infused CAR T-cell dose was 3×105/kg (range: 0.2-10×105/kg). The CAR-T/T-cell ratio and the CD19+ B lymphocyte percentage in PBLC samples from 159 of the patients were analyzed using flow cytometry on day 0, 4, 7, 11, 14, 21, and 30 following CAR T-cell infusion. We performed single continuous variate factors analysis on the influence of the CAR-T/T-cell ratio and the percentage of CD19 + B-lymphocytes in day 30 post-infusion PBLC samples on the OS, LFS, and CRR. We also analyzed the impact of patient age, BM blast count, CAR-T-cell dose, and the interval time between CAR-T-cell therapy and consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) on OS and LFS. Results Among 254 patients, 231 cases achieved CR within one month after CART therapy. A total of 211 CR patients had long-term follow-up of more than 30 days with a median follow-up of 12 months (1 to 29 months). On day 30 post CAR T-cell infusion, the median CAR-T/T-cell ratio in PBLC samples was 0.51% (range: 0%-44.8%), with 59 of 169 patients (34.9%) having a CAR-T/T-cell ratio of ≥1% and 85 of 169 patients (50.3%) with a CAR-T/T-cell ratio of ≥0.5%. The median percentage of CD19+ B lymphocytes in PBLC on day 30 was 0.0% (range: 0.0%-9.4%), of which 157 of 169 patients (92.9%) had Using a single continuous variate factors analysis, we found that increasing BM blasts and percentage of CD19+ B-lymphocytes in PBLC samples on day 30 correlated with a worse OS and LFS (Table 1). BM blasts of ≥70% were statistically significantly correlated with a worse OS and LFS when compared to BM blasts of The remaining 184 patients in CR received a consolidation allo-HSCT after a median interval time of 67 days post CAR T-cell therapy (range: 30-334 days). Thirty-two of these patients (17%) relapsed with a median time to relapse of 221 days (57-490 days). The remaining 27 patients received CAR T-cell therapy only and 11 (41%) relapsed with a median time to relapse of 100 days (53-398 days). None of the four factors above had an influence on the CRR in either the bridging into allo-HSCT group or the CAR-T only group (Table 2). Conclusions Using a single continuous variate factors analysis, we found that a high BM blast count and the percentage of CD19+ B-lymphocytes in PBLC samples from R/R ALL patients on day 30 predicted a worse OS and LFS while age, the CAR-T/T-cell ratio on day 30, CAR-T cell dose, and the interval time between CAR-T cell infusion and allo-HSCT had no clear impact on long-term outcomes. Disclosures No relevant conflicts of interest to declare.

Backgrounds Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has demonstrated 80-90% complete remission (CR) rate in R/R B-ALL; however, 10% to 20% of patients have no response and the potential etiology and risk factors remain unclear. Patients and Methods From Apr. 2017 to Mar. 2019, 254 patients with R/R B-ALL received treatment at our single center with a second-generation CD 19 CAR-T from 5 companies (NCT03173417; ChiCTR-ONC-17012829; NCT02546739; ChiCTR1800016541; and NCT03671460). The targeted median infused CAR-T cell dose was 3x105/kg. For all patients, screening was undertaken for 58 types of B-ALL related gene mutations and 49 congenital immune deficiency gene mutations using next generation sequencing (NGS) method. The patient and CAR-T product characteristics were analyzed to see if any factors affected the initial CR rate. Univariate analysis comparing CR rates between subgroups were carried out using chi-squared tests. Logistic regression model was adopted for multivariate analysis. Results On D30, 90.6% (230/254) patients achieved CR, and minimal residual disease (MRD)-negative CR was 89.4% (227/254). Univariate analysis (Table 1&2) showed a statistical difference in CR rate between females and males (84.54% vs. 94.27%, p=0.011). The CR rate of patients who received prior either CAR-T or blinatumomab treatment was lower than those who had not (50% vs. 91.53%, p=0.01). For the characteristic fusion genes, the CR rate in patients with MLL-AF4 was 80%, which was inferior to those with other or no fusion genes (P=0.041). For gene mutations, a lower CR rate was observed in patients with TP53 mutation compared to those with other or no mutations (72.73% vs. 92.11% vs. 94.39%, P=0.004). Presence of congenital immune deficiency gene mutations did not affect CR rate. Patients with >20% bone marrow (BM) blasts had a worse outcome than those with BM blasts≤20% (79.17% vs. 97.47%, p14 yr, patients with or without extramedullary disease (EMD), or patients receiving different chemotherapies between enrollment and CAR-T cells infusion on top of fludarabine and cyclophosphamide (FC) conditioning regimen. Cytokine release syndrome (CRS) and neurotoxicity had no effect on CR rate.There was a trend towards a lower CR rate in patients who received donor-derived CAR-T versus patient-derived CAR-T products (61.54% vs. 92.12%, p = 0.081). A lower CR rate was observed in patients who received CD28 costimulatory domain versus 4-1BB CAR-T products (77.27% vs. 91.70%, p=0.053). There was no difference in CR rate between patients infused with cell dose ≥3x105/kg vs. cell dose 2x104/kg. No CR difference was observed from different manufacturing companies. Moreover, 125/254 cases had available data for analysis on subsets of CAR-T cells including central memory T cells (Tcm), naive T cells and T memory stem cells (Tscm). Each group was divided into high- or low-level groups based on the median level. The CR rate was 92.19% vs. 88.52% in high and low Tcm groups, 92.31% vs. 88.33% in high or low naive group, and 89.80% vs.90.24% in high and low Tscm groups, respectively. No difference in CR between the groups were observed. Multivariate analysis was performed to investigate factors affecting achievement of CR (Table 3). Female group had lower odds of achieving CR after CAR-T therapy compared to male group [OR=0.232(95%CI 0.082-0.652)]. Compared to patients without TP53 mutation or only with other gene mutations, patients with TP53 mutation were more likely to have a low CR rate after CAR-T treatment [OR=4.511(95%CI 1.295-16.895)]. Patients with BM blast >20% had lower odds of achieving CR compared to those with BM blast ≤20% [OR=0.095 (95%CI 0.022-0.260)]. Treatment with CAR-T with CD28 as a costimulatory domain resulted lower odds of CR compared to treatment with CAR-T with 4-1BB [OR=7.141 (95%CI 1.722-29.612)]. Patients who developed severe neurotoxicity (grade 2-4) post CAR-T had higher odds of achieving CR compared to patients with grade 0-1 neurotoxicity [OR=34.796(95%CI 3.232-374.659)]. Conclusions In this analysis, we have observed that significant risk factors for not achieving CR after CD-19 CAR-T therapy include female gender, BM blasts more than 20%, a positive TP53 mutation, treatment with CD28 co-stimulatory domain vs 4-1BB CAR-T product, and mild as opposed to severe CAR-T related neurotoxicity. Disclosures No relevant conflicts of interest to declare.

With the rapid development of commercial space program, the constellations of low-orbit satellites continue to emerge. The use of satellite networks and terrestrial networks to construct a space-ground integrated network and provide users with seamlessly connected communication services has become a trend in the future. Due to the relative motion characteristics of satellites, existing routing technologies such as routing algorithms based on rule-based network topology can no longer meet the requirements for routing calculation in such a dynamic network topology. Based on the analysis of the routing strategies of existing typical satellite networks and the characteristics of satellite operation, this paper illustrates a multi-orbit hybrid satellite network routing algorithm based on detection and self-learning. The algorithm has a simple control process with high reliability. The simulation results show that the protocol has good network performance in terms of effective data transmission rate and data routing hops, and can support the design of routing protocols for multi-orbit mixed satellite networks.

Background Mantle cell lymphoma (MCL) is an incurable B cell-derived malignant tumor with a median overall survival of 4–5 years. Mer tyrosine kinase (MerTK) has been reported to be aberrantly expressed in leukemia, melanoma, and gastric cancer, and plays a pivotal role in the process of oncogenesis. This study assessed the role of MerTK in MCL for the first time. Methods Immunohistochemistry and western blot were performed to figure out expression of MerTK in MCL. MerTK inhibition by either shRNA or treatment with UNC2250 (a MerTK-selective small molecular inhibitor) was conducted in MCL cell lines. MCL-cell-derived xenograft models were established to evaluate the anti-tumor effects of UNC2250 in vivo. Results MerTK was ectopically expressed in four of six MCL cell lines. Sixty-five of 132 (48.9%) MCL patients showed positive expression of MerTK. MerTK inhibition by either shRNA or treatment with UNC2250 decreased activation of downstream AKT and p38, inhibited proliferation and invasion in MCL cells, and sensitized MCL cells to treatment with vincristine in vitro and doxorubicin in vitro and in vivo. UNC2250 induced G2/M phase arrest and prompted apoptosis in MCL cells, accompanied by increased expression of Bax, cleaved caspase 3 and poly (ADP-ribose) polymerase, and decreased expression of Bcl-2, Mcl-1 and Bcl-xL. Moreover, UNC2250 delayed disease progression in MCL-cell-derived xenograft models. Conclusions Our data prove that ectopic MerTK may be a novel therapeutic target in MCL, and further pre-clinical or even clinical studies of UNC2250 or new MerTK inhibitors are essential and of great significance. Electronic supplementary material The online version of this article (10.1186/s13045-018-0584-6) contains supplementary material, which is available to authorized users.

Table S1. Baseline characteristics of MCL patients receiving R-CHOP like regimens and their correlations with MerTK. Table S2. Information of antibodies applied in immunohistochemistry and western blot assays. Table S3. Combination index values of UNC2250 and Vincristine or Doxorubicin in Z-138 and Mino cells. (DOCX 28Â kb)

Supplementary Methods: Confocal immunofluorescence assays; RNA extraction, reverse transcription and Real-Time PCR. (DOCX 2252Â kb)

Figure S1. MerTK knockdown mediated by shMerTK 4 suppressed downstream signaling pathways and proliferation in MCL cells. Figure S2. MerTK inhibition by either shRNA or treatment with UNC2250 suppressed migration of MCL cells. Figure S3. The effects of UNC2250 on proliferation and apoptosis of MCL cells. Figure S4. Representative flow cytometry profiles for apoptosis assays in Z-138, Mino and JVM-2 cells. Figure S5. Representative flow cytometry profiles for cell cycle analysis in Z-138, Mino and JVM-2 cells. Figure S6. Proliferation of Z-138 and Mino cells was inhibited with increasing concentrations of vincristine or doxorubicin. Figure S7. Expression of microRNA-126, microRNA-335 and Gas6 in MCL cells. (DOCX 15Â kb)

Due to the problems of the new generation of video coding standard HEVC (High-Efficiency Video Coding), such as high computational complexity and the large computation, This paper proposes a fast inter-mode decision algorithm based on image texture features and by using Sobel operator the edge features are extracted from CU which is partitioned by simulation, and then the final partitioning size of CU is determined by the texture features contained in the current CU block of simulation partitioning. By using this method, both of the traverse layers of CU depth and the times of inter predictive coding are reduced. Thus the computational complexity of coding terminal is lowered effectively. The experimental results showed that, compared with inter-mode decision algorithm in HEVC standard, the time of this method is saved 45.35% on average with little loss of coding efficiency and PSNR

Since the improvement of high efficient video coding (HEVC) compression ratio is yet not studied completely, a new segmentation-based image compression coding frame is realized in this paper. The compression performance of this coding frame is further improved by taking the coding standard HEVC as a basic part of image compression, using the characteristics of HEVC intra coding and inter coding as well as segmentation. Combined with the traditional coding frame HEVC, the frame is to fully use the excellent compression performance of existing standard frames, thus, fundamentally, ensuring the compression performance of the frame is proposed. Experimental results show that, at low bitrate section, the compression performance of the frame proposed is much better than that of HEVC.

Backgrounds The failure of current Standard Short-Course Chemotherapy (SCC) in new and previously treated cases with tuberculosis (TB) was mainly due to drug resistance development. But little is known on the characteristics of acquired drug resistant TB during SCC and its correlation with SCC failure. The objective of the study is to explore the traits of acquired drug resistant TB emergence and evaluate their impacts on treatment outcomes. Methods A prospective observational study was performed on newly admitted smear positive pulmonary TB (PTB) cases without drug resistance pretreatment treated with SCC under China’s National TB Control Program (NTP) condition from 2008 to 2010. Enrolled cases were followed up through sputum smear, culture and drug susceptibility testing (DST) at the end of 1, 2, and 5 months after treatment initiation. The effect factors of early or late emergence of acquired drug resistant TB , such as acquired drug resistance patterns, the number of acquired resistant drugs and previous treatment history were investigated by multivariate logistic regression; and the impact of acquired drug resistant TB emergence on treatment failure were further evaluated. Results Among 1671 enrolled new and previously treated cases with SCC, 62 (3.7 %) acquired different patterns of drug resistant TB at early period within 2 months or later around 3–5 months of treatment. Previously treated cases were more likely to develop acquired multi-drug resistant TB (MDR-TB) (OR, 3.8; 95 %CI, 1.4–10.4; P = 0.015). Additionally, acquired MDR-TB cases were more likely to emerge at later period around 3-5 months after treatment starting than that of non-MDR-TB mainly appeared within 2 months (OR, 8.3; 95 %CI, 1.7–39.9; P = 0.008). Treatment failure was associated with late acquired drug resistant TB emergence (OR, 25.7; 95 %CI, 4.3–153.4; P

Li 2 Fe 1− x Mn x Si0 4 /C cathode materials were synthesized by mechanical activation-solid-state reaction. The effects of Mn-doping content, roasting temperature, soaking time and Li/Si molar ratio on the physical properties and electrochemical performance of the Li 2 Fe 1− x Mn x Si0 4 /C composites were investigated. The materials were characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM), charge–discharge tests and AC impedance measurements. SEM images suggest that the morphology of the Li 2 Fe 1− x Mn x Si0 4 /C composite is sensitive to the reaction temperature. Samples synthesized at different temperatures have different extent of agglomeration. Being charged–discharged at C /32 between 1.5 and 4.8 V, the Li 2 Fe 0.9 Mn 0.1 Si0 4 /C synthesized at the optimum conditions shows good electrochemical performances with an initial discharge capacity of 158.1 mAh g −1 and a capacity retention ratio of 94.3% after 30 cycles. AC impendence investigation shows Li 2 Fe 0.9 Mn 0.1 SiO 4 /C have much lower resistance of electrode/electrolyte interface than Li 2 FeSiO 4 /C.

Human T-cell leukemia virus type 1 (HTLV-1) – the first human retrovirus discovered by Gallo and colleagues in the late 1970s,1 is clinically associated with adult T-cell leukemia, tropical spastic paraparesis or HTLV-1 associated myelopathy, and several other chronic diseases.2–5 It is estimated that 20–30 million of the world population is infected with HTLV-1, and 5–10% of these infected individuals will develop HTLV-1 associated diseases.6,7 No effective treatment is currently available for HTLV-1 infection, making the virus a dangerous emerging pathogen as classified by CDC. Virally encoded proteases (PR) play an essential role in the life cycle of all retroviruses as viral assembly, maturation and replication necessitate proteolytic cleavage of Gag and Gag-Pro-Pol polyproteins into structural (matrix, capsid, and nucleocapsid) as well as functional (reverse transcriptase and integrase) proteins.8 This, along with the successful development of HIV-1 PR inhibitors for the treatment of AIDS, validates HTLV-1 PR as an attractive viral target for therapeutic intervention in HTLV-1 infection. HTLV-1 PR of 125 amino acid residues and HIV-1 PR of 99 amino acid residues are members of the aspartic acid protease family, and function as a structurally conserved homodimer.9 Aside from their significantly different substrate specificity and inhibition profile due to relatively low sequence identity,10 the two viral proteases differ in the C-terminal region. HTLV-1 PR C-terminally is elongated by 10 amino acid residues (P116EAKGPPVIL125) as compared with HIV-1 PR – an attribute shared only by leukemia virus proteases.11 Hayakawa et al. first reported in 1992 that while the very last five residues (P121PVIL125) were functionally dispensable, residues 116–120 (P116EAKG120) were required for the auto-processing activity of HTLV-1 PR.12 However, sequence alignment, structure modeling, and functional characterizations of truncation mutants of HTLV-1 PR suggest that the extra C-terminal residues exist as a flexible tail distal to the active site of the enzyme, thus playing limited structural or functional roles.10,12,13 This tenet recently received support from structural studies by Wlodawer and colleagues of a truncated HTLV-1 PR (1–116), which retained 60% of the catalytic activity of its full-length counterpart.14 Nevertheless, the controversy still remains as evidenced by a latest report in 2008 that deletion of residues 116–125 or 117–125 in HTLV-1 PR rendered the protease completely inactive.15 The authors attributed the lack of activity of HTLV-1 PR (1–115) or HTLV-1 PR (1–116) to its inability to dimerize. These conflicting findings triggered us to carry out comparative functional studies of a full-length protease and its C-terminally truncated form HTLV-1 PR (1–116), both of which were chemically synthesized using the native chemical ligation (NCL) technique pioneered by Kent and colleagues.16 Stepwise chemical syntheses of active bovine leukemia virus PR (1–126) and (1–116) were reported in 1992 and 1993,17,18 followed by the synthesis of HTLV-1 PR (1–125) first in 1997,19 and then in 2002.20 However, no comparative activity data were generated for those synthetic enzymes to allow the delineation of the functional effect of C-terminal truncation. Using three different peptide substrates, we demonstrated in this report that truncation of the extra C-terminal residues of HTLV-1 PR reduced the catalytic efficiency of the viral protease by tenfold and lowered its turnover number by twofold.

Co3O4/graphite composites were synthesized by precipitation of cobalt oxalate on the surface of graphite and pyrolysis of the precipitate, and the effects of graphite content and calcination temperature on the electrochemical properties of the composites were investigated. The samples were characterized by thermogravimetry and differential thermal analysis (TG/DTA), X-ray diffractometry (XRD), scanning electron microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and charge/discharge measurements. With increasing the graphite content, the reversible capacity of the Co3O4/graphite composites decreases, while cycling stability improves dramatically, and the addition of graphite obviously decreases the average potential of lithium intercalation/deintercalation. The reversible capacity of the composites with 50% graphite rises from 583 to 725 mA·h/g as the calcination temperature increases from 300 to 500 °C, and the Co3O4/graphite composites synthesized at 400 °C show the best cycling stability without capacity loss in the initial 20 cycles. The CV profile of the composite presents two couples of redox peaks, corresponding to the lithium intercalaction/deintercalation for graphite and Co3O4, respectively. EIS studies indicate that the electrochemical impedance decreases with increasing the graphite content.

Defensins are small, beta-sheet-rich, cationic peptides found in many organisms. All defensins have amphiphilic properties, which are central for antimicrobial activities of the proteins. The human genome encodes many defensin-line molecules, of which 10 have been characterized. Molecules of all known human defensins are stabilized by three intramolecular disulfide bonds arranged in a conserved pattern. To date, studies of human defensins indicate that these proteins are involved in various biological processes associated primarily with defensive and regulatory responses to infections by pathological agents. A comprehensive understanding of the multiple roles played by defensins within the immune system is greatly increased by reviewing the results of detailed structural studies. Emerging structural data, derived by the X-ray crystallography and the NMR spectroscopy in solution combined with functional studies; allow a rational understanding of the different activities of defensins and the mechanisms controlling these activities. Due to their well-established antimicrobial properties, defensins are also being investigated for their potential as therapeutics agents. Recently, increased effort has been focused on studies of the immunoregulatory properties of defensins, associated with their ability to bind and activate the G(i)-protein-coupled seven-transmembrane receptors. Comprehensive studies of defensins require development of simple, efficient, and inexpensive methods to generate these proteins and their derivatives in correctly folded form. This review highlights the current status of the sample generation methods, structural studies, and the structure-function relationships for human defensins.